Medscape - Indication-specific dosing for Detrol, Detrol LA (tolterodine), frequency-based adverse effects, comprehensive interactions, contraindications, pregnancy & lactation schedules, and cost information.

Myasthenia Gravis DETROL should be used with caution in patients with myasthenia gravis , a disease characterized by decreased cholinergic activity at the neuromuscular junction. However, the confidence intervals overlapped. Patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until the drug's effects have been determined. Carcinogenesis, Mutagenesis, Impairment Of Fertility Carcinogenicity studies with tolterodine were conducted in mice and rats.

Thus, tolterodine exposure in the carcinogenicity studies was 9- to fold higher than expected in humans. No increase in tumors was found in either mice or rats. No mutagenic effects of tolterodine were detected in a battery of in vitro tests, including bacterial mutation assays Ames test in 4 strains of Salmonella typhimurium and in 2 strains of Escherichia coli , a gene mutation assay in LY mouse lymphoma cells, and chromosomal aberration tests in human lymphocytes.

Tolterodine was also negative in vivo in the bone marrow micronucleus test in the mouse. Based on AUC values, the systemic exposure was about fold higher in animals than in humans. At these doses, the AUC values were about to fold higher than in humans.

Rabbits treated subcutaneously at a dose of 0. This dose did not result in any embryotoxicity or teratogenicity. The offspring regained the weight during the maturation phase.

It is not known whether tolterodine is excreted in human milk; therefore, Detrol should not be administered during nursing.

A decision should be made whether to discontinue nursing or to discontinue Detrol in nursing mothers. Pediatric Use Efficacy in the pediatric population has not been demonstrated. Two pediatric phase 3 randomized, placebo-controlled, double-blind, week studies were conducted using tolterodine extended release Detrol LA capsules. A total of pediatric patients on Detrol LA and on placebo aged 5—10 years with urinary frequency and urge urinary incontinence were studied.

The percentage of patients with urinary tract infections was higher in patients treated with Detrol LA 6. Aggressive, abnormal, and hyperactive behavior and attention disorders occurred in 2.

No differences in the safety profile of tolterodine were identified based on age, gender, race, or metabolism. The data described below reflect exposure to Detrol 2 mg bid in patients and to placebo in patients exposed for 12 weeks in five Phase 3, controlled clinical studies.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation.

Additive drowsiness may also occur, depending on the interacting agent. Moderate The therapeutic benefits of ambenonium may be diminished when coadministered with the antimuscarinics. When concurrent use cannot be avoided, monitor the patient for reduced ambenonium efficacy.

Major Avoid the concomitant use of amiodarone with other agents that prolong the QT interval, such as tolterodine. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.

Moderate Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like tolterodine are used concomitantly with psychiatric medications with anticholinergic effects such as amoxapine. Additive drowsiness may also occur. Major Due to the potential for QT prolongation and torsade de pointes TdP , caution is advised when administering clarithromycin with tolterodine.

Clarithromycin is associated with an established risk for QT prolongation and TdP. Tolterodine has also been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.

Pharmacokinetic studies of the use of tolterodine concomitantly with CYP3A4 inhibitors have not been performed. Major Torsades de pointes TdP and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy.

Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with anagrelide include tolterodine. Moderate Additive anticholinergic effects may be seen when tolterodine is used concomitantly with other antimuscarinics.

When possible, avoid concurrent use, especially in the elderly, who are more susceptible to the anticholinergic effects. Consider alternatives to these other medications, if available. Clinicians should note that antimuscarinic effects might be seen not only on bladder smooth muscle, but also on GI function, the eye, and temperature regulation.

Blurred vision, constipation, and dry mouth may be more prominent additive effects. With many of the listed agents, additive drowsiness may also occur when combined. Moderate Use caution if tolterodine and aprepitant, fosaprepitant are used concurrently and monitor for an increase in tolterodine-related adverse effects for several days after administration of a multi-day aprepitant regimen.

Tolterodine is a CYP3A4 substrate. As a single mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions.

However, as a single mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant mg IV as a single dose increased the AUC of midazolam given on days 1 and 4 by approximately 1.

Less than a 2-fold increase in the midazolam AUC is not considered clinically important. Moderate Caution is advised when administering aripiprazole with tolterodine, as use of these drugs together may increase the risk for QT prolongation and torsade de pointes TdP. QT prolongation has also occurred during therapeutic use of aripiprazole and following overdose. Major If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy.

QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes TdP and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with arsenic trioxide include tolterodine. Concomitant use warrants caution due to the potential for increased side effects. Furthermore, although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.

Concomitant use of artemether; lumefantrine with drugs that may prolong the QT interval, such as tolterodine, should be avoided. Consider ECG monitoring if tolterodine must be used with or after artemether; lumefantrine treatment.

Major Concurrent use of asenapine and tolterodine should be avoided due to an increased risk for QT prolongation and torsade de pointes TdP. Asenapine has also been associated with QT prolongation. CYP3A4 inhibitors include anti-retroviral protease inhibitors. In addition, ritonavir and delavirdine inhibit CYP2D6.

Moderate The plasma concentrations of tolterodine may be elevated when administered concurrently with cobicistat. A decreased dose may be warranted.

Clinical monitoring for adverse effects, such as dry mouth or QT prolongation, is recommended during coadministration. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously with tolterodine include atomoxetine.

QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of TdP. Agents that inhibit intestinal motility or prolong intestinal transit time have been rarely reported to induce toxic megacolon.

Tolterodine has been reported to cause dry mouth and constipation as potential side effects. Other anticholinergic and CNS effects may also be additive. Atropine; Hyoscyamine; Phenobarbital; Scopolamine: Major Due to a possible risk for QT prolongation and torsade de pointes TdP , azithromycin and tolterodine should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports.

Concurrent use may increase the risk of QT prolongation. Major Due to the potential for QT prolongation and torsade de pointes TdP , caution is advised when administering bedaquiline with tolterodine. Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG.

An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. Belladonna Alkaloids; Ergotamine; Phenobarbital: Moderate Monitor patients for signs of urinary retention or reduced gastric motility when opium is used concomitantly with an anticholinergic drug, such as tolterodine.

Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: Moderate Potential QT prolongation has been reported in limited case reports with metronidazole.

Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with metronidazole include tolterodine. Bismuth Subsalicylate; Metronidazole; Tetracycline: Moderate Close clinical monitoring is advised when administering tolterodine with boceprevir due to an increased potential for tolterodine-related adverse events.

If tolterodine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of tolterodine. Tolterodine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme.

Coadministration may result in elevated tolterodine plasma concentrations. However, this interaction has not been studied. Major Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval, such as tolterodine.

Additionally, monitor patients for signs of urinary retention or reduced gastric motility when buprenorphine is used concomitantly with an anticholinergic drug, such as tolterodine. Moderate Bupropion exhibits moderate anticholinergic effects. Clinicians should keep this in mind when using antimuscarinics and other medications with anticholinergic activity in combination with bupropion. Moderate Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug, such as tolterodine.

Major Conduct periodic monitoring with electrocardiograms ECGs and electrolytes if coadministration of ceritinib and tolterodine is necessary. Avoid coadministration of ceritinib with tolterodine in patients who are poor CYP2D6 metabolizers PM due to increased tolterodine exposure; if coadministration is unavoidable, monitor for tolterodine-related adverse reactions.

Major Concurrent use of chloroquine and tolterodine should be avoided due to an increased risk for QT prolongation and torsade de pointes TdP.

The need to coadminister these drugs should be done with a careful assessment of risks versus benefits. Chloroquine administration is associated with an increased risk of QT prolongation and TdP. Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: Major Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like tolterodine are used concomitantly with other antimuscarinics like most phenothiazines.

In addition, tolterodine is associated with dose-dependent prolongation of the QT interval, especially in poor metabolizers of CYP2D6. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine and should be used cautiously and with close monitoring with tolterodine.

Major Drugs that decrease GI motility may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts.

Examples of drugs that significantly decrease GI motility include the antimuscarinics. In one study, healthy subjects were examined for GI irritation following the administration of oral potassium for at least 7 days. Glycopyrrolate was coadministered to some subjects in order to study the additional effects of delayed gastric emptying.

Therefore, if oral potassium supplementation is necessary in a patient taking antimuscarinics, a liquid formulation should be considered. If a solid formulation is being prescribed, the patient should be counseled on strategies that can be used to avoid GI irritation such as taking potassium products only while seated or standing, remaining upright for 10 minutes after each dose, and ingesting each dose with plenty of fluids.

Drugs that are also associated with QT prolongation and have antimuscarinic properties that should be used cautiously and with close monitoring with tolterodine include ciprofloxacin. Severe Coadministration of cisapride and tolterodine is contraindicated due to the risk for serious adverse events, such as torsade de pointes TdP.

QT prolongation and ventricular arrhythmias, including TdP and death, have been reported with cisapride. Major Concurrent use of citalopram and tolterodine should be avoided due to an increased risk for QT prolongation and torsade de pointes TdP. If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. In addition, citalopram may inhibit the CYP2D6 metabolism of tolterodine in extensive metabolizers.

Citric Acid; Potassium Citrate: Major Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like tolterodine are used concomitantly with other antimuscarinics.

Other commonly used drugs with moderate to significant anticholinergic effects include clozapine. Drugs that are also associated with QT prolongation and have antimuscarinic properties that should be used cautiously and with close monitoring with tolterodine include clozapine. Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: Moderate Promethazine carries a possible risk of QT prolongation.

Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with promethazine include tolterodine, Codeine; Promethazine: Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with promethazine include tolterodine, Crizotinib: Major Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving crizotinib concomitantly with tolterodine.

An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs.

Crizotinib has been associated with concentration-dependent QT prolongation. Moderate Tolterodine should be used cautiously with cyclobenzaprine. Cyclobenzaprine is structurally similar to tricyclic antidepressants.

Tricyclic antidepressants have been reported to prolong the QT interval, especially when given in excessive doses or in overdosage settings. Cyclobenzaprine is associated with a possible risk of QT prolongation and torsades de pointes TdP , particularly in the event of acute overdose. In addition, additive anticholinergic effects may be seen during coadministration. Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: In addition, both ritonavir and tolterodine are associated with QT prolongation; concomitant use increases the risk of QT prolongation.

Major Monitor for evidence of QT prolongation during concurrent use of dasatinib and tolterodine. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Moderate Tolterodine has been associated dose-dependent prolongation of the QT interval.

Tolterodine should be used cautiously with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia SVT , ventricular tachycardia, heart block, and premature ventricular contractions PVCs have been reported.

Major Due to the potential for QT prolongation and torsade de pointes TdP , caution is advised when administering tolterodine with degarelix. Degarelix can also cause QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other QT prolonging drugs. Moderate Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as tolterodine, should be expected with concurrent use of delavirdine.

Clinically relevant QTc prolongation may occur with deutetrabenazine. Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with promethazine include tolterodine, Dextromethorphan; Quinidine: Major Use tolterodine and quinidine concomitantly with caution and close monitoring. Quinidine can inhibit the hepatic CYP2D6 isoenzyme, which may decrease the metabolism of tolterodine.

It is not known if dosage adjustments in tolterodine would be needed as the result of this interaction. In addition, tolterodine is associated with dose-dependent prolongation of the QT interval, especially in poor metabolizers of CYP2D6, and quinidine including dextromethorphan; quinidine is associated with an established risk of QT prolongation.

In addition, the anticholinergic effects of quinidine may be significant and may be enhanced when combined with tolterodine. Anticholinergic agents administered concurrently with quinidine may produce additive antivagal effects on AV nodal conduction. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known. CYP3A4 inhibitors include diltiazem. Major Tolterodine should be used cautiously and with close monitoring with disopyramide.

Disopyramide administration is associated with QT prolongation and torsades de pointes TdP. Tolterodine is associated with dose-dependent prolongation of the QT interval, especially in poor metabolizers of CYP2D6. In addition to its electrophysiologic effects, disopyramide exhibits clinically significant antimuscarinic anticholinergic properties.

These can be additive with tolterodine. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents. Severe Because of the potential for torsades de pointes TdP , use of tolterodine and dofetilide is contraindicated. Major Due to the potential for QT prolongation and torsade de pointes TdP , caution is advised when administering tolterodine with dolasetron.

Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses i.

Major Due to the potential for QT prolongation and torsade de pointes TdP , caution is advised when administering tolterodine with rilpivirine. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Hepatic Impairment Liver impairment can significantly alter the disposition of tolterodine immediate release. In a study of tolterodine immediate release conducted in cirrhotic patients Child-Pugh Class A and B , the elimination half-life of tolterodine immediate release was longer in cirrhotic patients mean, 7.

The clearance of orally administered tolterodine immediate release was substantially lower in cirrhotic patients 1. Gender The pharmacokinetics of tolterodine immediate release and 5-HMT are not influenced by gender. Mean C of tolterodine immediate release 1. Mean AUC values of tolterodine 6. The elimination half-life of tolterodine immediate release for both males and females is 2.

Race Pharmacokinetic differences due to race have not been established. ECG monitoring is recommended in the event of overdosage. A month-old child who ingested 5 to 7 tolterodine immediate release 2 mg tablets was treated with a suspension of activated charcoal and was hospitalized overnight with symptoms of dry mouth. The child fully recovered. Both urinary bladder contraction and salivation are mediated via cholinergic muscarinic receptors. After oral administration, tolterodine is metabolized in the liver, resulting in the formation of 5- hydroxymethyl tolterodine 5-HMT , the major pharmacologically active metabolite.

Both tolterodine and 5-HMT exhibit a high specificity for muscarinic receptors, since both show negligible activity or affinity for other neurotransmitter receptors and other potential cellular targets, such as calcium channels.

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